The present invention relates to a method for converting the enantiomers of .alpha.-lipoic acid into the racemic mixture of .alpha.-lipoic acid.
.alpha.-lipoic acid is also referred to in the literature as 1,2-dithiolane-3-pentanoic acid or thioctic acid. .alpha.-lipoic acid is widely distributed in plants and animals as a coenzyme of .alpha.-keto acid dehydrogenases; the naturally-occurring form has the D-configuration and can be represented by the structural formula ##STR1##
.alpha.-lipoic acid is pharmacologically active and possesses, among other features, antiphlogistic and antinociceptive (analgesic) as well as cytoprotective properties. An important medical indication is the treatment of diabetic polyneuropathy. In the case of the pure optical isomers of .alpha.-lipoic acid (D and L forms, that is, D-.alpha.-lipoic acid and L-.alpha.-lipoic acid), in contrast to the racemic mixture, the D-enantiomer is mainly antiphlogistic and the L-enantiomer is mainly antinociceptive (EP 0 427 247; CA 2,029,596); see also The Merck Index, 10th Edition, page 9165.
Known syntheses of the pure optical isomers of .alpha.-lipoic acid proceed, for example, via chiral precursors which are split in the course of the synthesis. Furthermore, the racemic .alpha.-lipoic acid can also be separated by conversion into salts of pure optical isomers of .alpha.-methylbenzylamine and crystallization, with the pure diastereomeric pair of salts first being isolated (U.S. Pat. No. 5,281,722 which is incorporated by reference in its entirety; DE 41 37 773.7). The disadvantage of the method cited is, however, that in each case the unwanted enantiomer as such can sometimes no longer be used therapeutically and the process of splitting to obtain the desired pure optical isomer of .alpha.-lipoic acid consequently becomes uneconomic.
The multiple stage method for preparing enantiomerically pure D(+) .alpha.-lipoic acid and L(-) .alpha.-lipoic acid avoids the splitting process but also proves to be inconvenient for commercial use (U.S. Pat. No. 4,772,727 which is incorporated by reference in its entirety; EP 0 261 336).